Ginkgo Biloba

Ginkgo Biloba

PEP Topic 
Cognitive Impairment
Description 

Ginkgo biloba is an extract from the leaves of the ginkgo biloba tree. It is an herbal medicine that has been used for multiple conditions and is generally well tolerated, but case reports suggest it should be used with caution in patients with blood clotting disorders and those on anticoagulants because gingko leaves are believed to contain compounds that thin blood. Gingko biloba has been examined for its effect on cognitive impairment in individuals with cancer.

Wong, C. (2012). Gingko—What you need to know. Retrieved April 1, 2013, from http://altmedicine.about.com/cs/herbsvitaminsek/a/Ginkgo.htm

Effectiveness Unlikely

Research Evidence Summaries

Attia, A., Rapp, S.R., Case, L.D., D'Agostino, R., Lesser, G., Naughton, M., . . . Shaw, E.G. (2012). Phase II study of Ginkgo biloba in irradiated brain tumor patients: Effect on cognitive function, quality of life, and mood. Journal of Neuro-Oncology, 109, 357–363.

doi:10.1007/s11060-012-0901-9
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Study Purpose:

To test the hypothesis that ginkgo biloba may be helpful for radiation-induced cognitive impairment

Intervention Characteristics/Basic Study Process:

120 mg ginkgo biloba was given for 24 weeks and then discontinued for 6 weeks as a washout period. Tests were administered at baseline, 12 weeks, 24 weeks, and 30 weeks after the initial evaluation.

Sample Characteristics:

  • The study reported on a sample of 34 patients with a median age of 47 years (range 22–82).
  • Participants were 32% male and 68% female.
  • Cognitive impairment and depressed mood were present in the sample at baseline.
  • All participants had brain irradiation six or more months prior to study entry and no evidence of disease progression.

Setting:

  • Single site
  • Outpatient    
  • North Carolina

Phase of Care and Clinical Applications:

Phases of Care: Late effects and survivorship

Study Design:

An open label phase II study design was used.

Measurement Instruments/Methods:

  • Mini mental state exam
  • Trail Making Test parts A and B
  • Digit Span Test
  • Revised Rey-Osterrieth Complex Figure Test
  • Verbal fluency (FAS) test
  • California Verbal Learning Test II
  • FACT-Brain
  • Profile of Mood States (POMS)

Results:

Trail Making Test (TMT) results improved significantly from baseline to 24 weeks; however, TMT-Part B continued to improve significantly from week 24 to week 30 after ginkgo was stopped. It is unclear if changes seen demonstrate improvement with treatment or learning effect. Scores for immediate and delayed recall on the Rey-Osterreith Figure were better (p < 0.0002), but these were not measured and reported at 30 weeks. There were no other changes in mental function scores. POMS scores improved for overall mood for the first 24 weeks and then began to decline. By 24 and 30 weeks, only 19 patients remained in the study. Most common toxicities reported were cognitive issues and memory problems. Five patients (16%) discontinued treatment because of gastrointestinal symptoms. One patient discontinued treatment because of intracranial bleed in one patient. Another five patients (16%) discontinued treatment because of no perceived benefit.

Conclusions:

Findings from the study do not provide clear support for the effectiveness of gingko biloba on cognitive impairment caused by brain irradiation.

Limitations:

  • The study had a small sample size with less than 30 participants.
  • A risk of bias was possible because there was no control group, no blinding, and no random assignment.
  • Findings were not generalizable.
  • Subject withdrawals were greater than or equal to 10% of participants.
  • There was a potential testing effect in the study.

Nursing Implications:

Findings do not support effectiveness of gingko biloba to improve cognitive function in patients who have impairment associated with brain radiation.

Barton, D.L., Burger, K., Novotny, P.J., Fitch, T. R., Kohli, S., Soori, G., . . . Loprinzi, C.L. (2013). The use of ginkgo biloba for the prevention of chemotherapy-related cognitive dysfunction in women receiving adjuvant treatment for breast cancer, N00C9. Supportive Care in Cancer, 21, 1185–1192.

DOI: 10.1007/s00520-012-1647-9
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Study Purpose:

Evaluate ginkgo biloba for the prevention of cognitive decline associated with adjuvant treatment for breast cancer

Intervention Characteristics/Basic Study Process:

Patients were randomized to receive 60 mg of ginkgo biloba or a matching placebo twice a day starting before the second cycle of thermotherapy and continuing throughout treatment and 1 month beyond chemotherapy completion. Participants were stratified by type of chemotherapy, age, menopausal status, and lymph node involvement. Data were collected at baseline before the first or second chemotherapy cycle, during chemotherapy, at the first visit after chemotherapy (1 month), and at 6, 12, 18, and 24 months post-chemotherapy.

Sample Characteristics:

  • A total of 210 participants were enrolled in the study.
  • The median age was 50 years.
  • The sample was 100% female.
  • All participants had newly diagnosed breast cancer and were chemotherapy naïve. 
  • All were receiving adjuvant chemotherapy. About 80% were receiving doxorubicin/cyclophosphamide with or without taxanes.
  • 42% of the women were post-menopausal. 
  • 94% of the women were Caucasian.

Setting:

  • Multi-site  
  • Outpatient 
  • 23 institutions in the United States

Phase of Care and Clinical Applications:

Participants were receiving active antitumor treatment.

Study Design:

Double-blind, randomized, placebo-controlled study

Measurement Instruments/Methods:

  • High-Sensitivity Cognitive Screen (HSCS)
  • Profile of Mood States (POMS)
  • Cognitive subscale of the Perceived Health Scale (PHS)
  • Common Terminology Criteria for Adverse Events (CTCAE) grading of adverse events
  • Trail Making Test (TMT) A and B

Results:

No significant differences were seen between groups over 24 months in any study measures. All cognitive test scores improved from baseline to the first chemotherapy follow-up and then stabilized.

Conclusions:

The study does not support the use of ginkgo biloba for prevention of cognitive impairment resulting from chemotherapy treatment in women with breast cancer.

Limitations:

  • A risk of bias existed because of the very homogenous sample.
  • The measurement validity and reliability was questionable because use of the same cognitive measures repeatedly could have resulted in improvement from practice effects.

Nursing Implications:

Findings do not support the use of ginkgo biloba to prevent cognitive changes resulting from chemotherapy in patients with breast cancer.

Systematic Review/Meta-Analysis

Chan, R.J., McCarthy, A.L., Devenish, J., Sullivan, K.A., & Chan, A. (2015). Systematic review of pharmacologic and non-pharmacologic interventions to manage cognitive alterations after chemotherapy for breast cancer. European Journal of Cancer, 51, 437–450. 

doi: 10.1016/j.ejca.2014.12.017
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Purpose:

STUDY PURPOSE: To review what is known about the effectiveness of pharmacologic and nonpharmacologic interventions for managing self-reported or objective cognitive impairment associated with chemotherapy for breast cancer
 
TYPE OF STUDY: Systematic review

Search Strategy:

DATABASES USED: MEDLINE, EBSCOhost, CINAHL, and Cochrane CENTRAL
 
KEYWORDS: Extensive list of terms, including keywords relevant to the receipt of chemotherapy, randomized controlled trials (RCTs), and cognitive impairment
 
INCLUSION CRITERIA: Prospective RCTs of pharmacologic or nonpharmacologic interventions to manage cognitive impairment during or after chemotherapy for cancer; subjective or objective measurement of cognitive function; published in English
 
EXCLUSION CRITERIA: Inclusion of patients with brain tumors or metastases; inclusion of patients not receiving chemotherapy; less than half of patients in sample diagnosed with breast cancers; unpublished RCTs; letters to the editor; retrospective chart reviews

Literature Evaluated:

TOTAL REFERENCES RETRIEVED: 29
 
EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Retrieved references were assessed by type of cancer (13 removed), cognitive impairment as an outcome (two removed), and confirmation of RCT (one removed). The Cochrane Collaboration risk of bias criteria were used to evaluate the final set of studies on randomization, blinding, and outcome reporting. Although effect sizes or relative risk were calculated for individual studies, a meta-analysis was not done because of the heterogeneity of the interventions and outcome measures.
 

Sample Characteristics:

  • FINAL NUMBER STUDIES INCLUDED = 13
  • TOTAL PATIENTS INCLUDED IN REVIEW = 1,138
  • SAMPLE RANGE ACROSS STUDIES = 20–210 patients
  • KEY SAMPLE CHARACTERISTICS: Most studies included only women with breast cancer. All participants received chemotherapy with or without radiation therapy or hormonal therapy. Most participants were aged about 55 years. The majority of studies were conducted in the United States. Most outcomes were evaluated in the short-term (i.e., less than three months).

Phase of Care and Clinical Applications:

PHASE OF CARE: Late effects and survivorship 

Results:

Risk of bias was high in 11 studies but unclear in  two studies that evaluated psychostimulants.

Pharmacologic interventions: No improvements in cognitive function were found using psychostimulants (four studies) or ginkgo biloba. Patients reported better cognitive function using epoetin alfa with doses titrated for hemoglobin levels (p < 0.05). However, a death caused by a cerebrovascular accident was noted.

Nonpharmacologic interventions: Small-group memory training improved self-reported cognitive function, and both memory and speed of processing after small-group training improved immediate and delayed recall (p < 0.05). Home-based online executive function training improved verbal function and attention (p < 0.05). Speed-feedback therapy during biking improved executive and motor function (p < 0.05). Cognitive behavioral therapy-based interventions (two studies), Tibetan sound meditation, and hatha yoga did not improve cognitive function.

Conclusions:

The pharmacologic studies reviewed did not support the use of psychostimulants or ginkgo biloba to improve cognitive function after chemotherapy for breast cancer. Epoetin alfa was not recommended for practice because of safety concerns. The nonpharmacologic studies reviewed provided some evidence that cognitive training and speed-feedback therapy might improve cognitive function for breast cancer survivors.

Limitations:

The risk of bias was high for most studies. Therefore, although positive results were found, well-designed, prospective RCTs need to be completed to confirm these findings. It is unclear how sustainable the positive results of the cognitive training and exercise interventions might be because follow-up was limited to less than three months.

Nursing Implications:

This systematic review provided limited support for cognitive training and structured exercise to improve cognitive function after chemotherapy for breast cancer. Cognitive training is currently categorized as likely to be effective for cognitive impairment.

Morean, D.F., O'Dwyer, L., & Cherney, L.R. (2015). Therapies for cognitive deficits associated with chemotherapy for breast cancer: A systematic review of objective outcomes. Archives of Physical Medicine and Rehabilitation, 96, 1880–1897. 

doi: 10.1016/j.apmr.2015.05.012
Print

Purpose:

STUDY PURPOSE: To evaluate the effectiveness of interventions for objectively measured cognitive impairments in women with breast cancer who received chemotherapy
 
TYPE OF STUDY: Systematic review

Search Strategy:

DATABASES USED: CINAHL, Cochrane, EMBASE, PsycINFO, and PubMed
 
KEYWORDS: Breast cancer, chemobrain, chemofog, chemotherapy, and several terms related to cognition and language deficits; appendix 1 described an extensive list of search terms and strategies that were used for PubMed and EMBASE
 
INCLUSION CRITERIA: Objective measurement of cognitive function; sample consisted of women with breast cancer who received or were receiving chemotherapy; experimental design (cross-sectional, longitudinal, or randomized clinical trials) 
 
EXCLUSION CRITERIA: Case studies or series, commentaries, editorials, dissertations not published in a peer-reviewed journal, systematic reviews, and meta-analyses

Literature Evaluated:

TOTAL REFERENCES RETRIEVED: 1,745
 
EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Abstracts were screened, and 30 duplicates were eliminated (plus 14 titles without abstracts). Abstracts were reviewed to validate that the studies involved women with breast cancer who were undergoing or received chemotherapy and that they had an objective neuropsychological assessment (1,556 articles excluded). The remaining articles (n = 145) were reviewed to ensure an that an intervention was administered for cognitive impairment (131 articles excluded) and that the studies met specific quality criteria as defined by the Physiotherapy Evidence Database rating scale criteria as well as criteria for treatment fidelity (two articles excluded).  

Sample Characteristics:

  • FINAL NUMBER STUDIES INCLUDED = 12
  • TOTAL PATIENTS INCLUDED IN REVIEW = 442
  • SAMPLE RANGE ACROSS STUDIES = 12–107 patients
  • KEY SAMPLE CHARACTERISTICS: Although education status may influence neuropsychological test results, only half of the studies provided this information. Likewise, menopausal status may affect cognition, and this was only reported by two thirds of the studies.

Phase of Care and Clinical Applications:

PHASE OF CARE: Late effects and survivorship

Results:

Studies of pharmacologic interventions were not found to be effective in improving cognitive function. Medications reviewed included d-methylphenidate (n = 1), epoetin alfa (n = 2), and ginkgo biloba (n = 1). Evidence for nonpharmacologic interventions was mixed. No improvements in cognitive function were found with Tibetan sound meditation (n = 1). Natural restorative therapy (n = 1) improved attention only when comparing the baseline with the final 90-day evaluation (p = 0.01). Exercise (n = 1) improved attention (p = 0.019) and verbal memory (p = 0.048) but not working memory. Cognitive rehabilitation (n = 1) improved four out of six measures of information processing speed (p < 0.05) but not attention, verbal memory, or executive function. Cognitive behavioral training (n = 2) improved verbal memory (p < 0.05) in both studies and was effective in improving in information processing speed when compared to baseline scores in one study (p ≤ 0.01) but not the other. Computerized cognitive training was effective in one study in improving processing speed (p = 0.009), executive function (p = 0.008), and a measure of executive function and language (p = 0.003) but not verbal memory. However, in another study, there was no difference in verbal memory or information processing speed between the intervention and control groups.

Conclusions:

Nonpharmacologic interventions, especially cognitive training, may have a role for improving attention, information processing speed, and verbal memory. Exercise and computerized cognitive training may be effective for improving executive function. However, additional research validating these findings with larger sample sizes and evaluating other cognitive domains is needed. In addition, studies determining the dose or duration of interventions is required for a durable response.

Limitations:

  • A small number of studies (n = 12) were included in the review for multiple types of interventions.
  • Only one study had a sample size greater than 100 (range = 12–107).
  • Studies of low quality were included. 

Nursing Implications:

These findings suggest that nonpharmacologic, not pharmacologic, interventions may be helpful in managing chemotherapy-induced cognitive impairment in patients with breast cancer. However, these findings were based on a small number of studies per intervention. Additional research validating which interventions might be useful in improving cognitive impairments in women receiving chemotherapy for breast cancer is needed. 

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